An interesting article caught my attention regarding the association between long-term proton pump inhibitor use and rates of dementia. Researchers from the University of Rostock in Germany analyzed over 73,000 medical records from an insurance database from 2004 to 2011. What they found was that patients receiving proton pump inhibitors (PPIs) for acid reflux were found to have significantly higher rates of dementia (44%).
My interest in this study comes from the fact that acid reflux and obstructive sleep apnea tend to go hand in hand. Obstructive episodes can create tremendous vacuum forces in the chest and throat cavities, literally suctioning up normal stomach juices into the esophagus and even the throat. Besides conservative recommendations, acid-reducing medications such as PPIs (various brands include Prilosec, Nexium, and Prevacid) are usually prescribed. All these medications work by blocking the proton pump in the acid-secreting cells in the stomach. Another class of medications includes the H2 blockers, with two common brand names seen is Tagamet or Zantac. These medications are sold over the counter, as well as by prescription. It’s estimated that the market value for acid reflux medications in 2016 was $5.66 billion.
Here are some of my comments and observations about this study:
- Mouse models have shown increased rates of beta-amyloid buildup in mice given PPIs.
- PPI use was shown to block the neurotransmitter acetylcholine, potentially leading to dementia.
- Untreated obstructive sleep apnea (OSA) is also associated with higher rates of dementia. In this Taiwanese insurance database study, there was an overall 1.7x increased risk of having dementia if you also had OSA. For older males (ages 50 to 59), the risk was 6x higher, and for older females (> 70), about 3x higher.
- In this prospective study, older women (average age 82) without dementia were found to develop higher rates of mild cognitive impairment (1.85x) if they had obstructive sleep apnea (AHI > 15).
- Intermittent hypoxia (low oxygen levels), which is commonly seen in patients with untreated obstructive sleep apnea has been shown to increase levels of beta-amyloid plaques in mice.
- Acid reflux medications do nothing to prevent acid reflux. Instead, they lower acid production in the stomach, rather than keeping stomach contents in the stomach. What comes up, however, still includes bile, bacteria, and digestive enzymes. Pepsin, a well-known stomach enzyme, has been found in the lung, ear and nasal/sinus areas.
It’s important to realize that all of the above-mentioned studies don’t prove cause and effect, but only associations. It’s hard to tease out if dementia and OSA have the same causes (leading to an association), or if needing to take a PPI to treat acid reflux is the consequence of someone already predisposed to reflux, OSA, and dementia.
Furthermore, there are countless studies on the documented side effects of short and long-term PPI use, including increased bone fractures, increased risk of pneumonia, and vitamin and mineral deficiencies.
But based on the numerous studies on this subject so far, I think it’s prudent to follow the precautionary principle, which states that given the paucity of definitive studies showing that PPI use is safe, it’s better to emphasize caution. My philosophy has always been to treat acid reflux by treating the underlying sleep-related breathing disorder, rather than covering up the acid reflux.